Jan L. Houghton

Heterogeneous Vasomotor Responses of Coronary Conduit and Resistance Vessels in Hypertension

OBJECTIVES The purpose of our study was to investigate the relation between conductance and resistance coronary vasomotor responsiveness in hypertensive patients without atherosclerosis. BACKGROUND Although similar in morphology, conduit and resistance coronary vessels differ importantly in size, function and local environment and appear to be differentially affected in certain disease processes, such as atherosclerosis and hypertension. However, little is known about the effect of hypertension on contiguous coronary conduit and resistance vessels in humans. METHODS Changes in coronary blood flow (a measure of resistance vessel reactivity) and coronary artery diameter (a measure of conduit vessel reactivity) were investigated in response to graded infusion of the endothelium-dependent agonist acetylcholine (ACh) in 98 patients with normal coronary arteries. RESULTS In 31 normotensive, euglycemic patients, conduit and resistance coronary artery responses to intracoronary infusion of ACh were significantly correlated (r = 0.73, p = 1 x 10[-6]), although eight patients (26%) had constriction of conduit but dilation of resistance arteries at peak effect. In 28 hypertensive patients without left ventricular hypertrophy (LVH), conduit and resistance artery responses to ACh remained significantly correlated (r = 0.5, p = 0.006), although 12 patients (43%) had discordant findings. Finally, in 39 hypertensive patients with LVH, conduit and resistance artery responses to ACh displayed the lowest correlation (r = 0.38, p = 0.02), with 22 patients (56%) demonstrating conduit artery constriction and resistance artery dilation. CONCLUSIONS Despite angiographically normal coronary arteries, heterogeneous vasomotor responses (dilation and constriction) were demonstrated in contiguous conduit and resistance arteries in normotensive and hypertensive patients referred for cardiac catheterization because of chest pain. In addition to more severe endothelial dysfunction among conduit and resistance arteries, a greater frequency of discordant conduit and resistance artery responses and resistance vessel constriction was found with increasing severity of hypertension. Our study suggests differing mechanisms of endothelium responsiveness to ACh among conduit and resistance coronary arteries.

Effect of African-American Race and Hypertensive Left Ventricular Hypertrophy on Coronary Vascular Reactivity and Endothelial Function

Excess cardiovascular morbidity and mortality among African (black) Americans remains an important yet unexplained public health problem. One possible explanation proposes that intrinsic or acquired abnormalities in coronary vascular reactivity and endothelial function result in excess ischemia among black Americans. To examine this hypothesis, we subjected 80 individuals with normal coronary arteries to invasive testing of coronary artery and microvascular relaxation using intracoronary infusions of acetylcholine and adenosine, a Doppler tipped intracoronary guide wire, and quantitative coronary angiography. We measured the percent increase in coronary blood flow and epicardial diameter after graded infusion of intracoronary acetylcholine and in coronary blood flow after intracoronary adenosine in 31 normotensive subjects (10 black, 21 white) and 49 hypertensive subjects with left ventricular hypertrophy (25 black, 24 white). Categorical and multivariate analyses revealed that in response to intracoronary adenosine and acetylcholine, the depression in endothelium-independent and -dependent microvascular relaxation during peak agonist effect was largely related to the presence of chronic hypertension and left ventricular hypertrophy. Normotensive subjects demonstrated no intrinsic racial differences in conduit and resistance vessel vasoreactivity. In response to maximal infusion of acetylcholine, epicardial coronary arteries constricted similarly in black and white subjects with hypertensive left ventricular hypertrophy and dilated similarly in normotensive black and white subjects. Thus, our study shows that in a cohort of black and white subjects referred for coronary arteriography because of chest pain, African American race is not associated with excess intrinsic or acquired depression in coronary vascular relaxation during the peak effect of the endothelium-dependent and -independent agonists acetylcholine and adenosine, after adjustment for the presence of left ventricular hypertrophy.

The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine☆

OBJECTIVES The purpose of our study was to determine if the presence of African American ethnicity modulates improvement in coronary vascular endothelial function after supplementary L-arginine. BACKGROUND Endothelial dysfunction is an early stage in the development of coronary atherosclerosis and has been implicated in the pathogenesis of hypertension and cardiomyopathy. Amelioration of endothelial dysfunction has been demonstrated in patients with established coronary atherosclerosis or with risk factors in response to infusion of L-arginine, the precursor of nitric oxide. Racial and gender patterns in L-arginine responsiveness have not, heretofore, been studied. METHODS Invasive testing of coronary artery and microvascular reactivity in response to graded intracoronary infusions of acetylcholine (ACh) +/- L-arginine was carried out in 33 matched pairs of African American and white subjects with no angiographic coronary artery disease. Pairs were matched for age, gender, indexed left ventricular mass, body mass index and low-density lipoprotein cholesterol. RESULTS In addition to the matching parameters, there were no significant differences in peak coronary blood flow (CBF) response to intracoronary adenosine or in the peak CBF response to ACh before L-arginine infusion. However, absolute percentile improvement in CBF response to ACh infusion after L-arginine, as compared with before, was significantly greater among African Americans as a group (45 +/- 10% vs. 4 +/- 6%, p = 0.0016) and after partitioning by gender. The mechanism of this increase was mediated through further reduction in coronary microvascular resistance. L-arginine infusion also resulted in greater epicardial dilator response after ACh among African Americans. CONCLUSIONS We conclude that intracoronary infusion of L-arginine provides significantly greater augmentation of endothelium-dependent vascular relaxation in those of African American ethnicity when compared with matched white subjects drawn from a cohort electively referred for coronary angiography. Our findings suggest that there are target populations in which supplementary L-arginine may be of therapeutic benefit in the amelioration of microvascular endothelial dysfunction. In view of the excess prevalence of cardiomyopathy among African Americans, pharmacologic correction of microcirculatory endothelial dysfunction in this group is an important area of further investigation and may ultimately prove to be clinically indicated.

Racial differences in myocardial ischemia and coronary flow reserve in hypertension

OBJECTIVES Using invasive measurements of endothelium-independent coronary flow reserve and stress thallium testing with or without dipyridamole, this study investigated racial differences in ischemia and coronary reserve in hypertensive left ventricular hypertrophy. BACKGROUND African Americans compared with Caucasian Americans appear to have a higher case fatality from coronary heart disease but lesser amounts of atherosclerotic coronary artery disease. This paradox may be explainable by intrinsic or acquired racial differences in coronary arteriolar autoregulation and vasoreactivity. METHODS The study enrolled 91 African and 81 Caucasian Americans referred for cardiac catheterization because of suspected myocardial ischemia but found to have no significant coronary stenosis. Patients were stratified by degree of left ventricular hypertrophy for comparison purposes after calculation of indexed left ventricular mass by means of echocardiographic M-mode measurements. Coronary flow reserve measurements were made using the intracoronary Doppler catheter and hyperemic doses of intravenous dipyridamole in 100 patients and intracoronary papaverine and adenosine in 72 patients. Seventy-seven percent of patients underwent adequate stress thallium testing with or without dipyridamole. RESULTS In African Americans, mean (+/- SD) coronary flow reserve decreased from 4.4 +/- 2.3 for 38 without mass hypertrophy to 3.2 +/- 1.3 for 53 with hypertrophy (p = 0.005) to 2.7 +/- 1.1 for 12 with severe hypertrophy (p = 0.02). Thallium testing was abnormal in 31% of those without mass hypertrophy and 59% of those with hypertrophy. In Caucasian Americans, coronary flow reserve decreased from 4.1 +/- 2 for 58 without hypertrophy to 3.6 +/- 1.5 for 23 with hypertrophy (p = NS) to 3 +/- 1.5 for 6 with severe hypertrophy (p = NS). Thallium testing was abnormal in 36% without mass hypertrophy and in 39% with hypertrophy. CONCLUSIONS This study establishes that development of left ventricular hypertrophy in hypertension carries greater physiologic morbidity for African compared with Caucasian Americans, typified by marked reduction in endothelium-independent coronary flow reserve and increased frequency of abnormal thallium tests.

African Americans With LVH Demonstrate Depressed Sensitivity of the Coronary Microcirculation to Stimulated Relaxation

Abstract—Excess coronary heart disease morbidity and mortality among African Americans remains an important yet unexplained public health problem. We hypothesized that adverse outcome is in part due to intrinsic or acquired abnormalities in coronary endothelial function and vasoreactivity. We compared dose-response curves relating changes in coronary blood flow and epicardial diameter to graded infusions of acetylcholine in 50 African American and 65 white subjects with hypertensive left ventricular hypertrophy (LVH) and normal coronary arteries. These groups were similar for age, body mass index, mean arterial pressure, and indexed left ventricular mass. The same protocol was conducted in 24 normotensive African American and 56 similar white subjects. We found significant depression in the coronary blood flow dose-response curve relation among African Americans when compared with white subjects with similar LVH (P <0.03). Racial differences were observed at all doses of acetylcholine but were less precisely estimated at the highest dose. The same testing among normotensive subjects revealed similar dose-response curves with no significant effect of race. Qualitatively similar results were found with respect to coronary diameter. Adenosine responses, a measure of endothelium-independent function, were similar after partitioning by LVH. Our study demonstrates that there are racial differences in sensitivity of coronary arteries to acetylcholine-stimulated relaxation among those with LVH. These results provide a mechanism whereby racial differences in coronary vasoreactivity might contribute to adverse coronary heart disease outcome among African Americans, a group in whom LVH is prevalent.

Pericarditis and myocarditis: Which is benign and which isn't?

Pericarditis and myocarditis are inflammatory diseases that are often initiated by common viruses. Pericarditis rarely causes serious long-term disability, whereas myocarditis may lead to chronic congestive cardiomyopathy and permanent disability. The pathogenesis of both is proposed to be bimodal, with an early stage characterized by viral replication and a later stage by infiltration of lymphocytes and necrosis of cells secondary to an autoimmune process. Treatment of pericarditis is usually symptomatic. Myocarditis requires bed rest and conventional therapy for congestive heart failure. Efficacy of immunosuppressive therapy for myocarditis is currently being tested in an international multi-center clinical trial.

A brief office educational intervention improved referral rates for hypertension control in women

As part of an initiative to increase physician awareness about hypertension and cardiovascular disease (CVD); we studied the effects of a pilot intervention on the rates of referral for uncontrolled hypertension in an Ob-Gyn office. Physicians in an Ob-Gyn practice completed an educational session regarding hypertension and used a 1-page tracking form in their medical records for 3 months. Trained personnel reviewed medical records to compare baseline rates of hypertension control to those at the end of the intervention. Rates of counseling about lifestyle modification to control hypertension were also documented. The rate of referral for hypertension was significantly increased after 3 months (p<0.001). The rates of counseling about CVD risk factors approached 100%. In this study, hypertension was commonly under-treated, despite being a major risk factor for CVD. As primary care physicians, obstetrician-gynecologists are in an excellent position to facilitate evaluation and treatment of hypertension in women. Education about the importance of hypertension control along with a simple tracking form can assist Ob-Gyn physicians in complying with JNC 7 guidelines.

Coronary vasomotor reactivity among normotensive African and white American subjects with chest pain

BACKGROUND AND OBJECTIVES Excess cardiovascular morbidity and mortality among African (black) Americans is the subject of intensive investigation but the etiology remains speculative. One hypothesis proposes that inherent, or intrinsic, differences in coronary vascular reactivity and endothelial function predispose African Americans to enhanced vasoconstriction and/or depressed vasodilation, resulting in excess ischemia. The objective of this study was to establish whether coronary vasoreactivity differs among normotensive, nondiabetic African and white Americans with normal arteries referred for coronary arteriography because of chest pain. PATIENTS AND METHODS Eleven African American (8 female, 3 male) and 28 white American (9 female, 19 male) normotensive, euglycemic patients with normal coronary arteries were prospectively recruited for invasive testing of coronary artery and microvascular relaxation using the endothelium-dependent and -independent agents, acetylcholine and adenosine; a Doppler tipped intracoronary guidewire; and quantitative coronary angiography. RESULTS The study cohort consisted of 17 women (44%) and 22 men (56%) with a mean age of 46 +/- 10 yrs. Of 8 African American women, 6 were premenopausal and 2 were postmenopausal on estrogen replacement therapy. Of 9 white American women, 2 were premenopausal, 1 was 46-year old with a previous history of hysterectomy without ovariectomy, 2 were postmenopausal on estrogen replacement therapy, 2 were perimenopausal and 44- and 54-year old, and 2 were postmenopausal without estrogen replacement therapy. In response to maximal infusion of acetylcholine, epicardial coronary arteries and resistance vessels dilated similarly in black and white subjects. Dose-response curves revealed no significant racial differences during submaximal graded infusion of acetylcholine. In response to peak effect of adenosine, there were no racial differences in dilation of the microcirculation. CONCLUSIONS In the absence of hypertension, diabetes mellitus, and angiographic evidence of coronary artery disease, African American women demonstrate no evidence of intrinsic predisposition to enhanced coronary conduit vasoconstriction or depressed microcirculatory dilation in response to the endothelium-dependent and -independent vasodilator agonists-acetylcholine and adenosine-when compared with responses of similar white men and women. Because of low enrollment of black males, definitive conclusions cannot be drawn regarding this group.

Left ventricular free wall rupture during coronary intervention after acute myocardial infarction: report of two cases exhibiting fatal pseudocomplications.

Two cases of left ventricular free wall rupture occurring in temporal relation to interventional coronary procedures are presented as autopsy‐verified pseudocomplications. The possible impact of pseudocomplications on operator‐specific registry data and credentialing is briefly discussed. Cathet. Cardiovasc. Intervent. 47:67–72, 1999.

Coronary vasomotor function in a normotensive, nondiabetic referral population with normal coronary arteriograms

In a referral normal cardiac population, endothelium-independent coronary relaxation is nearly always normal, but endothelium-dependent relaxation may be depressed in a significant proportion of patients. Further study of the natural history of referral subjects with endothelial dysfunction is necessary to assess the potential cardiovascular risk of this finding in a presumed low-risk population.